Although genetically inherited dystrophies are usually associated with degeneration of mature tissues, the elusive primary defect(s) in these diseases may be more amenable to identification in embryonic tissues in the absence of gross degeneration which may complicate the interpretation of results obtained with older tissues. This approach will be tested using a well-established cell culture system to compare the development of dispersed embryonic breast muscle cells obtained from normal and genetically dystrophic chick embryos. Skeletal muscle development in vitro, as well as in vivo, proceeds throough distinct stages culminating in the fusion of mononucleated myogenic cells into multinucleated myotubes which develop striations and become contractile. Since the cell surface or plasma membrane must play a key role in muscle development, viz. cell recognition and cell fusion, and since there has been considerable speculation that the primary defect in genetic dystrophy of muscle resides in the plasma membrane, we will compare the surface membranes of normal and genetically dystrophic cells as a function of development. Various culture techniques will be utilized to synchronize the development process and enrich cultures for cells at specific stages of development. At each of these developmental stages, plasma membranes will be isolated from both normal and genetically dystrophic cells, and the composition, metabolic turnover and spatial distribution or topography of the membrane components will be compared. In addition, we will examine the developmental consequences of altered membrane structure induced by manipulation of the culture medium. It is anticipated that these studies will 1) provide a better understanding of the role of the plasma membrane in muscle cell development; 2) provide information about the primary defect(s) in genetically dystrophic muscle; and 3) provide new information on the mechanism of naturally occurring membrane fusion.